Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus)

Abstract

Cotton rats (Sigmodon hispidus) were inoculated intranasally with 102.0 to 1010.0 PFU of human adenovirus type 5. The virus replicated to a high titer in pulmonary tissues, with the peak titer being proportional to the input dose. The 50% lethal dose was 109-4 PFU. Histopathologic changes were proportional to the infecting inoculum and included the infiltration of interstitial and intra-alveolar areas, moderate damage to bronchiolar epithelium, and cellular infiltration of peribronchiolar and perivascular regions. These changes could be divided into two phases: an early phase (affecting alveoli, bronchiolar epithelium, and peribronchiolar regions) with an infiltrate consisting primarily of monocytes-macrophages and neutrophils, with occasional lymphocytes, and a later phase (affecting peribronchiolar and perivascular regions) with an infiltrate consisting almost exclusively of lymphocytes. In both phases, the predominant process was the response of the host to infection, rather than direct viral damage to infected cells. An infecting inoculum of 108.0 PFU or larger caused severe damage to type II alveolar cells, which were swollen, showed a loss of lamellar bodies, and were surrounded by polymorphonuclear leukocytes and macrophages. No evidence of complete viral replication was found in type II alveolar cells.

Outcomes of Early Administration of Cidofovir in Non-Immunocompromised Patients with Severe Adenovirus Pneumonia

“…The pathophysiology of AdV pneumonia remains unclear; few studies have been performed. For example, Prince et al [34] and Gregory et al [35] indicated that much of the acute damage in adenovirus infection appears to be due to dysregulation of the immune system. These features may, in part, explain the self-limiting nature of cases of even severe AdV infection without antiviral therapy, and suggest that the host's immunological reaction to the infection is a major factor in the pathogenesis of the lung injury.…”

INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies

“…Although animal models other than the mouse have been explored, these models are only semipermissive, expensive or difficult to work with. [35][36][37][38][39][40][41][42][43] Our laboratory has recently developed the golden Syrian hamster (Mesocricetus auratus) as a permissive, immunocompetent animal model for efficacy studies of oncolytic Ad vectors 44,45 and as a model for Ad pathogenicity and testing of anti-Ad drugs. 46 We now report the first comprehensive biodistribution study of an oncolytic Ad vector in the Syrian hamster model.…”

T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders

“…Immune responses to adenovirus infection are dependent on primary sites of inoculation, methods of transmission, viral serotypes, and secretory Ig antibody status of the infected host; IgAs are present in respiratory tract early following infection, and IgG2 is present in serum and nasal secretions at later time points, reviewed in Walls et al (2003). Histopathological changes resulting from infection can be divided into two phases: The first phase of immune histopathology predominantly involves nonspecific, cytokine-mediated inflammatory recruitment of monocytes and macrophages, while the second phase involves T cell infiltration (Prince et al, 1993). T cellemediated immunity is believed to be required for HadV recovery from acute infections, and individuals lacking adaptive immunity are found to be at elevated risk of infection, with CD8 þ T cells as primary mediators of response to respiratory viruses, with relatively little contribution by CD4 þ cells (Woodland et al, 2001).…”